A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p < 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p < 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p < 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p < 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

Studies of the structure and function of a fibrinogen binding MSCRAMM(RTM) from Staphylococcus epidermidis

Coagulase-negative staphylococci (CNS) are recognized as important pathogens and are particularly associated with foreign body infections. S. epidermidis accounts for approximately 75% of the infections caused by CNS. Three genes, sdrF, sdrG, and sdrH, were identified by screening a S. epidermidis genomic library with a probe encompassing the serine-aspartate dipeptide repeat-encoding region (region R) of clfA from S. aureus. SdrG has significant amino acid identity to ClfA, ClfB and other surface proteins of S. aureus. SdrG is also similar to a protein (Fbe) recently described by Nilsson, et al. (Infection and Immunity, 1998, 66:2666–73) from S. epidermidis. The N-terminal domain (A region) of SdrG was expressed as a his-tag fusion protein in E. coli. In an ELISA, this protein, rSdrG(50-597) was shown to bind specifically to fibrinogen (Fg). Western ligand blot analysis showed that SdrG binds the Bβ chain of Fg. To further characterize the rSdrG(50-597)-Fg interaction, truncates of the Fg Bβ chain were made and expressed as recombinant proteins in E. coli. SdrG was shown to bind the full-length Bβ chain (1462), as well as the N-terminal three-quarters (1-341), the N-terminal one-half (1-220) and the N-terminal one-quarter (1-95) Bβ chain constructs. rSdrG(50-597) failed to bind to the recombinant truncates that lacked the N-terminal 25 amino acid residues of this polypeptide suggesting that SdrG recognizes a site within this region of the Bβ chain. Inhibition ELISAs have shown that peptide mimetics, including β1–25, and β6–20, encompassing this 25 residue region can inhibit binding of rSdrG(50-597) to Fg coated wells. Using fluorescence polarization we were able to determine an equilibrium constant (KD) for the interaction of rSdrG(50-597) with the Fg Bβ chain peptide β1–25. The labeled peptide was shown to bind to rSdrG(50-597) with a KD of 0.14 ± 0.01μM. Because rSdrG(50-597) recognizes a site in the Fg Bβ chain close to the thrombin cleavage site, we investigated the possibility of the rSdrG(50-597) site either overlapping or lying close to this cleavage site. An ELISA showed that rSdrG(50-597) binding to thrombin-treated Fg was significantly reduced. In a clot inhibition assay rSdrG(50-597) was able to inhibit fibrin clot formation in a concentration dependent manner. Furthermore, rSdrG(50-597) was able to inhibit clot formation by preventing the release of fibrinopeptide B as determined by HPLC. To further define the interaction between rSdrG(50-597) and peptide β6–20, we utilized an alanine amino acid replacement strategy. The residues in β6–20 that appear to be important in rSdrG(50-597) binding to Fg, were confirmed by the rSdrG(273-597)-β6–20 co-crystal structure that was recently solved by our collaborators at University of Alabama-Birmingham. Additionally, rSdrG(50-597) was not able to bind to Fg from different animal species, rather it bound specifically to human Fg in an ELISA. This suggests that the sequence variation between Fg Bβ chains of different species, specifically with in the N-terminal 25 residues, affects the ability of rSdrG(50-597) binding to Fg, and this may explain why S. epidermidis is primarily a human pathogen. ^

La objeción de conciencia y la negativa a brindar atención de salud reproductiva: un informe que examina la prevalencia, las consecuencias de salud y las respuestas normativas

Antecedentes: Global Doctors for Choice, una red transnacional de médicos defensores de la salud y los derechos reproductivos, comenzó a investigar el fenómeno de la negativa a prestar atención sanitaria por razones de conciencia debido a la cantidad creciente de informes de daños en todo el mundo. Este informe examina la prevalencia y el impacto de dicha negativa y revisa los esfuerzos normativos realizados para equilibrar la conciencia individual, la autonomía en la toma de decisiones sobre asuntos reproductivos, la salvaguardia de la salud y la integridad profesional médica. Objetivos y estrategia de búsqueda: Este informe tiene como base diversos materiales científicos médicos, legales, éticos, sociales y de salud pública publicados entre 1998 y 2013 en inglés, francés, alemán, italiano, portugués y español. Es difícil obtener estimaciones de prevalencia, dado que no existe consenso sobre los criterios para describir el estatus de objetor ni una definición normalizada de la objeción de conciencia como práctica, y también porque los estudios utilizados tienen limitaciones de muestreo y otros problemas metodológicos. El informe analiza esa información y ofrece marcos de referencia lógicos para representar las consecuencias que supone para la salud y el sistema de salud la práctica de la objeción de conciencia a proporcionar servicios de aborto, tecnologías de reproducción asistida, tratamiento de anticoncepción en casos de riesgo de la salud materna y pérdida inevitable del embarazo, y diagnóstico prenatal. Y en último lugar se presenta la categorización de las respuestas legales y regulatorias, así como otras respuestas normativas a la práctica. Conclusiones: La evidencia empírica es esencial, dado que los diversos actores políticos responden con políticas o reglamentaciones para equilibrar las posiciones en conflicto. Es necesario realizar más investigación y capacitación en diversos contextos geopolíticos. Partiendo del doble compromiso con la propia conciencia y con la obligación de velar por la salud y los derechos de las pacientes, exhortamos a proveedores, profesionales sanitarios y asociaciones de salud pública a promover acciones que respondan a la práctica de la objeción de conciencia a prestar atención sanitaria y permitan salvaguardar la salud reproductiva, la integridad médica y las vidas de las mujeres.